It has been estimated that there are more than 18 million cases of sepsis per year, with the mortality rate in severe cases making it the second leading cause of deaths in non-coronary intensive care units. See, e.g., Dellinger, et al., Crit. Care Med, 37(11):2929-2938 (2009), incorporated by reference; Dellinger, et al., Crit. Care Med, 36(1):296-327 (2008), also incorporated by reference; Marshall, et al., J Infect. Diseases, 190:527-534 (2004), also incorporated by reference.
Broadly defined, “sepsis” refers to the presence of a systemic inflammatory response resulting from bacterial infection. In turn, a systemic inflammatory response is defined as the presence of two or more abnormalities in body temperature, heart rate, respiratory rate or blood gas, and an abnormal white blood cell count. “Severe sepsis” results from dysfunction of one or more organs as a result of the response to the above infection, while “septic shock” occurs with the development of cardiovascular instability, including hypotension, also resulting from a response to the above infection. The term “severe septic shock” includes both severe sepsis and septic shock.
When “sepsis” is used herein, all of the above conditions are encompassed thereunder.
Approaches to treating sepsis include, inter alia, administration of intravenous fluids, antibiotics, vasopressors, and steroids. None have been very successful and in the case of steroids, therapeutic approaches are controversial. Notwithstanding these approaches, as Dellinger et al. (2009), supra, reports, mortality remains high, and a large medical need remains unmet.
U.S. Pat. No. 5,674,855 to Levine, et al., the disclosure of which is incorporated by reference describes emulsions of various materials, which showed efficacy in treatment of endotoxemia. In brief, the emulsions contain a phospholipid (phosphatidylcholine), a neutral lipid (triglyceride), and a cholate salt (sodium cholate). Various ranges of the materials in relationship to each other are described. The patent discloses a process for making the emulsion, as well as methods for the intravenous administration thereof. A product based upon these formulations, referred to as “GR270773,” was tested for efficacy in dialysis patients with endotoxemia (see www.clinicaltrials.gov, identifier NCT00506454), and in a very widespread trial reported by Dellinger (2009), supra. The dialysis trial showed no efficacy whatsoever, and the clinical trial reported by Dellinger et al., supra concluded that the emulsion did not show efficacy greater than treatment with a placebo.
It has now been found, however, that emulsions of the type described in the '855 patent do in fact have surprising efficacy in a subset of patients, as defined herein. Such a result was not to be expected from the literature which concluded that the emulsions were ineffective.
Details of this invention are set forth in the Detailed Description of Preferred Embodiments which follows.